Hydrogen sulfide (H2S), once identified exclusively as a pernicious toxic gas, is now recognized as a key participant in a myriad of physiological functions. Activity occurs in a wide variety of systems including periodontal, cardiovascular, neurological, inflammatory, and gastrointestinal. We have selected one of these areas and propose new research for examining the role of H2S in gastrointestinal illness including colitis, irritable bowel syndrome, and Crohn's disease. Our planned approach focuses on the development of a rapid, optical method for measuring hydrogen sulfide concentrations in exhaled breath. We anticipate that, by the end of the Phase II grant, we will have demonstrated in a clinical setting a compact, fully-automated instrument that can report H2S real-time concentration profiles with fast response times within individual exhalations. Detection sensitivity will be 50 ppb or better. Fast response will allow the H2S mouth contributions to be resolved temporally for alveolar contributions. Our Overall Hypothesis is that a portable easy to use breath hydrogen sulfide monitor can be developed to diagnose and manage irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Our Specific Aim is to evaluate breath collected from patients with IBS and IBD to healthy controls, and compare the results to validated instruments such as symptom questionnaires and standard hydrogen and methane breath analysis. The proposed exhaled H2S analysis method uses an optical spectroscopy technique call noise-immune, cavity-enhanced, optical heterodyne measurement spectroscopy (NICE-OHMS). The technique was invented about 15 years ago by John Hall and co-workers at NIST. It can achieve extraordinary detection sensitivity for a variety of gases, but has been considered too difficult for commercial applications. We recently simplified NICE-OHMS by using low-cost, low-power electronics developed for wireless networking. Reliable gas commercial analyzers can now be built. NICE-OHMS should be useful for breath analysis. It works well with small gas samples (~50 std. cc per exhalation) and has fast time response. Fully engineered analyzers will be about the size of a desktop computer. PUBLIC HEALTH RELEVANCE: Breath analysis has the potential to become a widely-used, rapid method for therapeutic monitoring. Our proposed project focuses on detection of hydrogen sulfide in breath as a way of monitoring and developing treatments for debilitating gastrointestinal diseases such as irritable bowel syndrome, inflammatory bowel disease and Crohn's disease.